Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs

• Published in: PLoS pathogens Vol. 7; no. 9; p. e1002262
• Main Authors: Subbian, Selvakumar, Tsenova, Liana, O'Brien, Paul, Yang, Guibin, Koo, Mi-Sun, Peixoto, Blas, Fallows, Dorothy, Dartois, Veronique, Muller, George, Kaplan, Gilla
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.09.2011; Public Library of Science (PLoS)
• Subjects: Animals; Antibiotics; Antitubercular Agents - therapeutic use; Bacteria; Bacterial Load; Biology; Chemistry; Cyclic AMP - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism; Deoxyribonucleic acid; DNA; Drug Resistance, Bacterial; Experiments; Female; Gene expression; Gene Expression Regulation; Genetic aspects; Health aspects; Immune system; Infections; Isoniazid - therapeutic use; Lung - immunology; Lung - microbiology; Lung - pathology; Lungs; Macrophages - immunology; Male; Medicine; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - immunology; Oligonucleotide Array Sequence Analysis; Phosphodiesterase 4 Inhibitors - therapeutic use; Phosphodiesterases; Physiological aspects; Rabbits; Standard deviation; Thalidomide - analogs & derivatives; Thalidomide - therapeutic use; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - genetics; Tuberculosis - microbiology; Tuberculosis - pathology; Tumor Necrosis Factor-alpha - biosynthesis; Veterinary Science; United States

Tuberculosis (TB) treatment is hampered by the long duration of antibiotic therapy required to achieve cure. This indolent response has been partly attributed to the ability of subpopulations of less metabolically active Mycobacterium tuberculosis (Mtb) to withstand killing by current anti-TB drugs....